Coating solutions comprising surface active segmented block copolymers

ABSTRACT

This invention is directed toward surface treatment of a device. The surface treatment comprises the placing of surface active segmented block copolymers to the surface of the substrate. The present invention is also directed to a surface modified medical device, examples of which include contact lenses, intraocular lenses, vascular stents, phakic intraocular lenses, aphakic intraocular lenses, corneal implants, catheters, implants, and the like, comprising a surface made by such a method.

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of Provisional Patent ApplicationNo. 61/016,844 filed Dec. 27, 2007; Provisional Patent Application No.61/016,845 filed Dec. 27, 2007; Provisional Patent Application No.61/016,841 filed Dec. 27, 2007; and Provisional Patent Application No.61/016,843 filed Dec. 27, 2007.

FIELD OF INVENTION

This invention relates to coating solutions comprising a new class oftailored polymers useful as surface coatings for ophthalmic devices.These polymers can be specifically tailored using controlled radicalpolymerization processes and contain a number of functional domains.Controlled radical polymerization allows the facile synthesis ofsegmented block copolymers with tunable chemical composition that, as aresult, show different chemical properties than those prepared viaconventional free radical polymerization. Surface active segmented blockcopolymers show good surface properties when associated with substrates.

BACKGROUND OF THE INVENTION

Medical devices such as ophthalmic lenses are made from a wide varietyof materials. In the contact lens field materials are broadlycategorized into conventional hydrogels or silicone hydrogels. Recently,the use of silicone-containing materials (silicone hydrogels) has beenpreferred. These materials can vary greatly in water content. However,regardless of their water content, silicone materials tend to berelatively hydrophobic, non-wettable, and have a high affinity forlipids. Methods to modify the surface of silicone devices by increasingtheir hydrophilicity and improving their biocompatibility are of greatimportance.

A number of copolymers for surface coatings have been investigated. U.S.Pat. No. 6,958,169 discloses providing a medical device formed from amonomer mixture comprising a hydrophilic device-forming monomerincluding a copolymerizable group and an electron donating moiety, and asecond device-forming monomer including a copolymerizable group and asurface active functional group; and, contacting a surface of themedical device with a wetting agent including a proton donating moietyreactive with the functional group provided by the second lens-formingmonomer and that complexes with the electron donating moiety provided bythe hydrophilic lens-forming monomer.

U.S. Pat. No. 6,858,310 discloses a method of modifying the surface of amedical device to increase its biocompatibility or hydrophilicity bycoating the device with a removable hydrophilic polymer by means ofreaction between reactive functionalities on the hydrophilic polymerwith functionalities that are complementary on or near the surface ofthe medical device.

U.S. Pat. No. 6,599,559 discloses a method of modifying the surface of amedical device to increase its biocompatibility or hydrophilicity bycoating the device with a removable hydrophilic polymer by means ofreaction between reactive functionalities on the hydrophilic polymerwhich functionalities are complementary to reactive functionalities onor near the surface of the medical device.

U.S. Pat. No. 6,428,839 discloses a method for improving the wettabilityof a medical device, comprising the steps of: (a) providing a medicaldevice formed from a monomer mixture comprising a hydrophilic monomerand a silicone-containing monomer, wherein said medical device has notbeen subjected to a surface oxidation treatment; (b) contacting asurface of the medical device with a solution comprising aproton-donating wetting agent, whereby the wetting agent forms a complexwith the hydrophilic monomer on the surface of the medical device in theabsence of a surface oxidation treatment step and without the additionof a coupling agent.

Many copolymers are currently made using conventional free radicalpolymerization techniques with the structure of the polymer beingcompletely random or controlled by the reactivity ratios of therespective monomers. By using controlled free radical polymerizationtechniques one is able to assemble copolymers in a controlled fashionand, in turn, they show completely different solution and coatingproperties than copolymers prepared using conventional free radicalpolymerization techniques. Controlled free radical polymerization can beconducted by a variety of methods, such as ATRP (atom transfer radicalpolymerization) and RAFT (Reversible addition-fragmentation chaintransfer polymerization).

There are a number of commercially available block copolymer surfactantsthat can function as antifoaming agents, wetting agents, dispersants,thickeners, and emulsifiers. One such surfactant class is the Pluronic®and Tetronic® block copolymers based on ethylene oxide and propyleneoxide, available from BASF. Another class of surfactants is the Silwet®and Silsoft® block copolymers based on ethylene oxide and siloxaneblocks, available from GE silicones. These block copolymers and avariety of others rely on ring opening polymerization methods to producethe blocks.

With the advent and rapid growth of RAFT polymerization in the late1990's, block copolymers can now be prepared from a wide variety ofvinyl based monomers. This opens up the toolbox for polymer chemists tosynthesize countless number of block copolymer compositions. Inaddition, for the construction of surfactants there is a lot of chemicaldiversity in the selection of both the hydrophobic moieties and thehydrophilic moieties.

Surfactants or “surface active agents” lower the surface tension ofwater or other liquids and concentrate at the surface of the liquid.Surfactants have a common structural feature in which one portion of thesurfactant molecule is highly polar or even ionic (hydrophilic or waterloving) and the other portion is largely non-polar (hydrophobic or waterfearing). The relationship of these two structural parts of the moleculewith respect to each other controls the properties of the surfactant.

SUMMARY

This particular invention is related to the synthesis and preparation ofspecifically tailored block copolymer surfactants where both the lengthsof the individual blocks, the chemical composition, and the sequencedistribution are carefully controlled and the affinity of thesesurfactants for specific substrates can be guided by the “like preferslike” principle. For example, fluorocarbons interact with higheraffinity to other fluorine-containing materials, as well as siliconecontaining blocks will interact with higher affinity to siliconecontaining materials. Therefore in one embodiment of this invention, ablock copolymer surfactant is prepared via RAFT polymerization thatcontains a hydrophilic block (NVP or DMA), and a fluorine containinghydrophobic block (perfluoroacrylate), where the surfactant is used totreat a fluorine containing substrate (i.e. Teflon or afluoroelastomer). In another embodiment, a block copolymer surfactant isprepared via RAFT polymerization that contains a hydrophilic block (NVPor DMA), and a silicone containing hydrophobic block (TRIS-VC orM1-MCR-C12), where the surfactant is used to treat a silicone containingsubstrate (i.e. silicone hydrogel or a silicone elastomer).

In still another embodiment of this invention, a block copolymersurfactant is prepared via RAFT polymerization that contains ahydrophilic block (NVP or DMA), and a hydrocarbon containing hydrophobicblock (Hexyl methacrylate or lauryl methacrylate), where the surfactantis used to treat a hydrocarbon based substrate (i.e. polyethylene orpolypropylene). Disclosed in certain preferred embodiments herein is amethod of forming a surface modified medical device, the methodcomprising providing a medical device having at least one surface;providing a surface modifying agent comprising a surface activesegmented block copolymer; and contacting the at least one surface ofthe medical device with the surface modifying agent to form a surfacemodified medical device.

Also disclosed herein is a surface modified medical device comprising amedical device and a surface active segmented block copolymer comprisinga hydrophobic unit block comprising vinylically unsaturatedpolymerizable monomers and a hydrophilic block comprising vinylicallyunsaturated polymerizable monomers applied to the surface of the medicaldevice.

Further in accordance with the present disclosure, the invention relatesgenerally to coating solutions comprising surface active segmented blockcopolymers for forming coatings in the manufacture of medical devices.Examples of suitable devices include of heart valves, intraocularlenses, intraocular lens inserter, contact lenses, intrauterine devices,vessel substitutes, artificial ureters, vascular stents, phakicintraocular lenses, aphakic intraocular lenses, corneal implants,catheters, implants, endoscopic instruments, artificial breast tissueand the like.

Surface active segmented block copolymers prepared through Atom TransferRadical Polymerization (“ATRP”) methods in accordance with the inventionherein have the following generic formula (I):

R₁-[(A)_(m)]_(p)-[(B)_(n)]_(q)—X   (I)

wherein R₁ is the reactive residue of a moiety capable of acting as aninitiator for Atom Transfer Radical Polymerization, A is a hydrophobicunit block, B is a hydrophilic unit block, m is 1 to 10,000, n is 1 to10,000, p and q are natural numbers, and X is a halogen capping group ofthe initiator for Atom Transfer Radical Polymerization. It should benoted that there are many processes for the post polymerization removalor transformation of the halogen capping group of an initiator for AtomTransfer Radical Polymerization which are known to one of ordinary skillin the art. Therefore polymers prepared using ATRP according to theinvention herein would include those where X is a halogen capping groupof the initiator for Atom Transfer Radical Polymerization and thosepolymers that have undergone post polymerization removal ortransformation of the halogen capping group of an initiator for AtomTransfer Radical Polymerization (i.e., derivatized reaction product).The polymers which contain halogen end-groups can be utilized in a hostof traditional alkyl halide organic reactions. In one example, theaddition of tributyltin hydride to the polymeric alkyl halide in thepresence of a radical source (AIBN, or Cu(I) complex) leads to asaturated hydrogen-terminated polymer. In another example, by replacingtributyltin hydride with allyl tri-n-butylstannane, polymers with allylend groups can be prepared. The terminal halogen can also be displacedby nucleophilic substitution, free-radical chemistry, or electrophilicaddition catalyzed by Lewis acids to yield a wide variety of telechelicderivatives, such as alkenes, alkynes, alcohols, thiols, alkanes,azides, amines, phosphoniums, or epoxy groups, to mention a few.

Surface active segmented block copolymers prepared through Reversibleaddition-fragmentation chain transfer polymerization (“RAFT”) methods inaccordance with the invention herein have the following generic formula(II):

R₁-[(A)_(m)]_(p)-[(B)_(n)]_(q)—R₂   (II)

wherein R₁ is a radical forming residue of a RAFT agent or free radicalinitiator, A is a hydrophobic unit block, B is a hydrophilic unit block,m is 1 to 10,000, n is 1 to 10,000, p and q are natural numbers, and R₂is a thio carbonyl thio fragment of the chain transfer agent. RAFTagents based upon thio carbonyl thio chemistry are well known to thoseof ordinary skill in the art and would include, for example, xanthates,trithiocarbonates and dithio esters. It should be noted that there aremany processes for the post polymerization removal or transformation ofthe thio carbonyl thio fragment of the chain transfer agent which areknown to one of ordinary skill in the art. Therefore polymers preparedusing RAFT agent according to the invention herein would include thosewhere R₂ is a thio carbonyl thio fragment of the chain transfer agentand those polymers that have undergone post polymerization removal ortransformation of the thio carbonyl thio fragment of the chain transferagent (i.e., a derivatized reaction product). One example of such atransformation is the use of free radical reducing agents to replace thethio carbonyl thio group with hydrogen. Others include thermolysis ofthe end group or conversion of the thio carbonyl thio groups to thiolgroups by aminolysis. A wide variety of telechelic derivatives can beprepared, such as alkenes, alkynes, alcohols, thiols, alkanes, azides,amines, phosphoniums, or epoxy groups, to mention a few.

Surface active segmented block copolymers prepared through reversibleaddition-fragmentation chain transfer polymerization (“RAFT”) methods inaccordance with the invention herein have the following generic formula(III):

R1-[(B)n]q-[(A)m]p-R2-[(A)m]p-[(B)n]q-R1   (III)

wherein R1 is a radical forming residue of a RAFT agent or free radicalinitiator, A is a hydrophobic unit block, B is a hydrophilic unit block,m is 1 to 10,000, n is 1 to 10,000, p and q are natural numbers, and R2is a thio carbonyl group.

For each of the polymers of generic formula I, II and III the order ofthe block units is not critical and the surface active segmented blockcopolymer can contain more than two blocks. Therefore the surface activesegmented block copolymers can be multiblock copolymers and includerepetition of one or more blocks. As examples please see the nonlimitingrepresentations below, each of which is intended to fall within genericformula I, II and III:

-(A)_(m)-(B)_(n)—  (1)

—(B)_(n)-(A)_(m)-   (2)

-(A)_(m)-(B)_(n)-(A)m-   (3)

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic example of atom-transfer radical polymerization(ATRP) used to make a segmented block copolymer in which there is anoligomeric block of the hydrophobic unit at one end of the polymerfollowed by a large hydrophilic block;

FIG. 2 is the structural formula of various monomers which may be usedto provide the hydrophobic unit of the segmented block copolymers of theinvention herein;

FIG. 3 is a reaction schematic showing how RAFT polymerization can beused to polymerize block copolymers with surface active domains.

DETAILED DESCRIPTION

The present invention relates generally to coating solutions comprisingsurface active segmented block copolymers. Compositions comprising thesurface active segmented block copolymers are useful in providingsurface bound coatings in the manufacture of medical devices. Inpreferred embodiments, the present invention relates to medical devicessurface coated with surface active segmented block copolymers. It shouldbe understood that the term “surface” as used to describe surfacecoating is not to be limited to meaning “at least one complete surface”.Surface coverage does not have to be even or complete to be effectivefor surface functionality. The surface active segmented block copolymersof the present invention are useful as coatings for biocompatiblematerials including both soft and rigid materials commonly used forophthalmic lenses, including contact lenses.

Therefore, disclosed in certain preferred embodiments herein is a methodof forming a surface modified medical device, the method comprisingproviding a medical device having at least one surface; providing asurface modifying agent comprising a surface active segmented blockcopolymer; and contacting the at least one surface of the medical devicewith the surface modifying agent to form a surface modified medicaldevice.

Also disclosed herein is a surface modified medical device comprising amedical device; and a surface active segmented block copolymercomprising a hydrophobic unit block and a hydrophilic block applied tothe surface of the medical device.

Further in accordance with the present disclosure, the invention relatesgenerally to coating solutions comprising surface active segmented blockcopolymers for forming coatings in the manufacture of medical devices.Examples of suitable devices include of heart valves, intraocularlenses, intraocular lens inserter, contact lenses, intrauterine devices,vessel substitutes, artificial ureters, vascular stents, phakicintraocular lenses, aphakic intraocular lenses, corneal implants,catheters, implants, endoscopic instruments, artificial breast tissueand the like.

Surface active segmented block copolymers prepared through Atom TransferRadical Polymerization (“ATRP”) methods in accordance with the inventionherein have the following generic formula (I):

R₁-[(A)_(m)]_(p)-[(B)_(n)]_(q)—X   (I)

wherein R₁ is the reactive residue of a moiety capable of acting as aninitiator for Atom Transfer Radical Polymerization, A is a hydrophobicunit block, B is a hydrophilic unit block, m is 1 to 10,000, n is 1 to10,000, p and q are natural numbers, and X is a halogen capping group ofthe initiator for Atom Transfer Radical Polymerization. It should benoted that there are many processes for the post polymerization removalor transformation of the halogen capping group of an initiator for AtomTransfer Radical Polymerization which are known to one of ordinary skillin the art. Therefore polymers prepared using ATRP according to theinvention herein would include those where X is a halogen capping groupof the initiator for Atom Transfer Radical Polymerization and thosepolymers that have undergone post polymerization removal ortransformation of the halogen capping group of an initiator for AtomTransfer Radical Polymerization (i.e., derivatized reaction product).The polymers which contain halogen end-groups can be utilized in a hostof traditional alkyl halide organic reactions. In one example, theaddition of tributyltin hydride to the polymeric alkyl halide in thepresence of a radical source (AIBN, or Cu(I) complex) leads to asaturated hydrogen-terminated polymer. In another example, by replacingtributyltin hydride with allyl tri-n-butylstannane, polymers with allylend groups can be prepared. The terminal halogen can also be displacedby nucleophilic substitution, free-radical chemistry, or electrophilicaddition catalyzed by Lewis acids to yield a wide variety of telechelicderivatives, such as alkenes, alkynes, alcohols, thiols, alkanes,azides, amines, phosphoniums, or epoxy groups, to mention a few.

Surface active segmented block copolymers prepared through Reversibleaddition-fragmentation chain transfer polymerization (“RAFT”) methods inaccordance with the invention herein have the following generic formula(II):

R₁-[(A)_(m)]_(p)-[(B)_(n)]_(q)—R₂   (II)

wherein R₁ is a radical forming residue of a RAFT agent or free radicalinitiator, A is a hydrophobic unit block, B is a hydrophilic unit block,m is 1 to 10,000, n is 1 to 10,000, p and q are natural numbers, and R₂is a thio carbonyl thio fragment of the chain transfer agent with theproviso that when A is an ionic block, B will be a nonionic block. Itshould be noted that there are many processes for the postpolymerization removal or transformation of the thio carbonyl thiofragment of the chain transfer agent which are known to one of ordinaryskill in the art. Therefore polymers prepared using RAFT agent accordingto the invention herein would include those where R₂ is a thio carbonylthio fragment of the chain transfer agent and those polymers that haveundergone post polymerization removal or transformation of the thiocarbonyl thio fragment of the chain transfer agent (i.e., a derivatizedreaction product). One example of such a transformation is the use offree radical reducing agents to replace the thio carbonyl thio groupwith hydrogen. Others include thermolysis of the end group or conversionof the thio carbonyl thio groups to thiol groups by aminolysis. A widevariety of telechelic derivatives can be prepared, such as alkenes,alkynes, alcohols, thiols, alkanes, azides, amines, phosphoniums, orepoxy groups, to mention a few.

Surface active segmented block copolymers prepared through reversibleaddition-fragmentation chain transfer polymerization (“RAFT”) methods inaccordance with the invention herein have the following generic formula(III):

R1-[(B)n]q-[(A)m]p-R2-[(A)m]p-[(B)n]q-R1   (III)

wherein R1 is a radical forming residue of a RAFT agent or free radicalinitiator, A is a hydrophobic unit block, B is a hydrophilic unit block,m is 1 to 10,000, n is 1 to 10,000, p and q are natural numbers, and R2is a thio carbonyl thio group.

For each of the polymers of generic formula I, II and III the order ofthe block units is not critical and the surface active segmented blockcopolymer can contain more than two blocks. Therefore the surface activesegmented block copolymers can be multiblock copolymers and includerepetition of one or more blocks. As examples please see the nonlimitingrepresentations below, each of which is intended to fall within genericformula I, II and III:

-(A)_(m)-(B)_(n)—  (1)

—(B)_(n)-(A)_(m)-   (2)

-(A)_(m)-(B)_(n)-(A)_(m)-   (3)

The present invention provides materials useful for surface modifyingcontact lenses and like medical devices through the use of surfaceactive functionality. Although only contact lenses will be referred tohereinafter for purposes of simplicity, such reference is not intendedto be limiting since the subject method is suitable for surfacemodification of other medical devices such as phakic and aphakicintraocular lenses and corneal implants as well as contact lenses. Thepreferred surface active segmented block copolymers in the presentinvention are selected based on the polymeric material to be coated.

The surface active segmented block copolymer comprises a hydrophobicunit block. The hydrophobic unit block can be made of vinylicallyunsaturated polymerizable monomers. Examples of hydrophobic vinylicallyunsaturated polymerizable monomers would include alkyl acrylates such ashexyl methacrylate and lauryl methacrylate, fluoroacrylates such asoctofluoropentamethacrylate and3,3,4,4,5,5,6,6,7,7,8,8-tridecafluorooctyl methacrylate (TDFM) andpolysiloxanylalkyl(meth)acrylic monomers such as TRIS-VC and M1-MCR-C12.The hydrophobic unit block can be varied and is selected based upon theintended use of the surface active segmented block copolymers. That is,the hydrophobic unit block of the surface active segmented blockcopolymers is selected to provide a composition that is complementarywith the surface of the device.

Selection of the hydrophobic unit monomer of the block copolymer isdetermined by the surface of the device. For example, if the surfaceactive molecule on the surface of the device contains perfluorinatedhydrocarbons, a monomer containing fluoroalkyl substituents (i.e.octafluoropentyl methacrylate) can be a hydrophobic unit monomer of thesurface active segmented block copolymer. If the surface active moleculeon the surface of the device contains siloxane functionality, siliconecontaining monomers (i.e. TRIS-methacrylate or TRIS-VC) can be ahydrophobic unit monomer of the surface active segmented blockcopolymer. A wide variety of suitable combinations of functional groupcontaining monomers of the hydrophobic unit complementary to the surfaceof the device will be apparent to those of ordinary skill in the art.

Generic structures of hydrophobic units would include the following:

wherein R can consist of alkyl, fluoroalkyl, siloxy, or branchedsilicone.

Non-limiting examples would include methacryloxypropyltris(trimethylsiloxy)silane or tris(trimethylsiloxy)silylpropylmethacrylate, 3-(trimethylsilyl)propyl vinyl carbonate;3-(vinyloxycarbonylthio)propyl-[tris(trimethylsiloxy)silane];3-[tris(trimethylsiloxy)silyl]propyl vinyl carbamate;3-[tris(trimethylsiloxy)silyl]propyl allyl carbamate;3-[tris(trimethylsiloxy)silyl]propyl vinyl carbonate; hexylmethacrylate, dodecyl methacrylate, lauryl methacrylate, hexyl vinylcarbamate, hexyl vinyl carbonate, octafluoropentamethacrylate, andoctafluoropenta vinyl carbamate.

The hydrophobic unit block of the surface active segmented blockcopolymers is oligomeric or polymeric and is sized to provide suitableassociation with the surface of the medical device to be coated.Therefore the variable m of formula I, II or III can be between 1 andabout 1000, preferably between 1 and about 100, most preferably between1 and about 30.

In addition to the hydrophobic unit, the surface active segmented blockcopolymers of the invention herein will also contain hydrophilicdomain(s) showing good surface properties when the block copolymer iscoated onto the substrates. The hydrophilic domain(s) can be made ofvinylically unsaturated polymerizable monomers such as, HEMA, glycerolmethacrylate, methacrylic acid (“MAA”), acrylic acid (“AA”),methacrylamide, acrylamide, N,N′-dimethylmethacrylamide, orN,N′-dimethylacrylamide; copolymers thereof; hydrophilic prepolymers,such as ethylenically unsaturated poly(alkylene oxide)s, cyclic lactamssuch as N-vinyl-2-pyrrolidone (“NVP”), or derivatives thereof. Stillfurther examples are the hydrophilic vinyl carbonate or vinyl carbamatemonomers. Hydrophilic monomers can be nonionic monomers, such as2-hydroxyethyl methacrylate (“HEMA”), 2-hydroxyethyl acrylate (“HEA”),2-(2-ethoxyethoxy)ethyl(meth)acrylate, glyceryl(meth)acrylate,poly(ethylene glycol(meth)acrylate), tetrahydrofurfuryl(meth)acrylate,(meth)acrylamide, N,N′-dimethylmethacrylamide,N,N′-dimethylacrylamide(“DMA”), N-vinyl-2-pyrrolidone (or other N-vinyllactams), N-vinyl acetamide, and combinations thereof. Still furtherexamples of hydrophilic monomers are the vinyl carbonate and vinylcarbamate monomers disclosed in U.S. Pat. No. 5,070,215, and thehydrophilic oxazolone monomers disclosed in U.S. Pat. No. 4,910,277. Thecontents of these patents are incorporated herein by reference. Thehydrophilic monomer also can be an anionic monomer, such as2-methacryloyloxyethylsulfonate salts. Substituted anionic hydrophilicmonomers, such as from acrylic and methacrylic acid, can also beutilized wherein the substituted group can be removed by a facilechemical process. Non-limiting examples of such substituted anionichydrophilic monomers include trimethylsilyl esters of (meth)acrylicacid, which are hydrolyzed to regenerate an anionic carboxyl group. Thehydrophilic monomer also can be a cationic monomer selected from thegroup consisting of 3-methacrylamidopropyl-N,N,N-trimethyammonium salts,2-methacryloyloxyethyl-N,N,N-trimethylammonium salts, andamine-containing monomers, such as 3-methacrylamidopropyl-N,N-dimethylamine. Other suitable hydrophilic monomers will be apparent to oneskilled in the art.

The hydrophilic monomer block will be sized to provide the desirablesurface coating property of the surface active segmented blockcopolymer. The size of the hydrophilic oligomeric or polymeric block mayvary depending upon the substrate to be coated and the intended use.Therefore the variable n of formula I, II or III can be between 1 andabout 10000, preferably between about 10 and about 1000, and morepreferably between about 20 and about 300.

Atom-transfer radical polymerization (ATRP) can be used to preparesegmented block copolymers in which the molecular weight of each of theblocks and the entire polymer can be precisely controlled. As shown inFIG. 1, atom-transfer radical polymerization (ATRP) can be used to makea surface active segmented block copolymer in which there is a block ofthe hydrophobic unit at one end of the polymer followed by a largehydrophilic block. It should be understood that the order of addition ofthe monomer comprising the hydrophobic unit domain and the monomercomprising the hydrophilic domain is not critical. A large number ofmonomers are available for the assembly of polymers (For example, seeFIG. 2). Reversible addition-fragmentation chain transfer polymerization(RAFT) can also be used to prepare segmented block copolymers in whichthe molecular weight of each of the blocks and the entire polymer can beprecisely controlled (see FIG. 3).

The surface active segmented block copolymers of the invention hereinare useful in providing coatings for substrates. Examples of substratematerials useful with the present invention are taught in U.S. Pat. No.5,908,906 to Künzler et al.; U.S. Pat. No. 5,714,557 to Künzler et al.;U.S. Pat. No. 5,710,302 to Künzler et al.; U.S. Pat. No. 5,708,094 toLai et al.; U.S. Pat. No. 5,616,757 to Bambury et al.; U.S. Pat. No.5,610,252 to Bambury et al.; U.S. Pat. No. 5,512,205 to Lai; U.S. Pat.No. 5,449,729 to Lai; U.S. Pat. No. 5,387,662 to Künzler et al.; U.S.Pat. No. 5,310,779 to Lai and U.S. Pat. No. 6,891,010 to Künzler et al.;which patents are incorporated by reference as if set forth at lengthherein.

The present invention contemplates the use of surface active segmentedblock copolymers with medical devices including both “hard” and “soft”contact lenses. As disclosed above, the invention is applicable to awide variety of materials. Hydrogels in general are a well-known classof materials that comprise hydrated, cross-linked polymeric systemscontaining water in an equilibrium state. Silicon containing hydrogelsgenerally have water content greater than about 5 weight percent andmore commonly between about 10 to about 80 weight percent. Suchmaterials are usually prepared by polymerizing a mixture containing atleast one silicon containing monomer and at least one hydrophilicmonomer. Typically, either the silicon containing monomer or thehydrophilic monomer functions as a crosslinking agent (a crosslinkerbeing defined as a monomer having multiple polymerizablefunctionalities) or a separate crosslinker may be employed. Applicablesilicon containing monomeric units for use in the formation of siliconcontaining hydrogels are well known in the art and numerous examples areprovided in U.S. Pat. Nos. 4,136,250; 4,153,641; 4,740,533; 5,034,461;5,070,215; 5,260,000; 5,310,779; and 5,358,995.

Examples of applicable silicon-containing monomeric units include bulkypolysiloxanylalkyl(meth)acrylic monomers. An example of bulkypolysiloxanylalkyl(meth)acrylic monomers are represented by thefollowing Formula IV:

wherein:

-   X denotes —O— or —NR—;-   each R₁ independently denotes hydrogen or methyl;-   each R₂ independently denotes a lower alkyl radical, phenyl radical    or a group represented by

wherein each R′_(2′) independently denotes a lower alkyl or phenylradical; and h is 1 to 10. Some preferred bulky monomers aremethacryloxypropyl tris(trimethyl-siloxy)silane ortris(trimethylsiloxy)silylpropyl methacrylate, sometimes referred to asTRIS.

Another class of representative silicon-containing monomers includessilicon containing vinyl carbonate or vinyl carbamate monomers such as:1,3-bis[4-vinyloxycarbonyloxy)butyl]tetramethyl-disiloxane;3-(trimethylsilyl)propyl vinyl carbonate;3-(vinyloxycarbonylthio)propyl-[tris(trimethylsiloxy)silane];3-[tris(tri-methylsiloxy)silyl]propyl vinyl carbamate;3-[tris(trimethylsiloxy)silyl]propyl allyl carbamate;3-[tris(trimethylsiloxy)silyl]propyl vinyl carbonate;t-butyldimethylsiloxyethyl vinyl carbonate; trimethylsilylethyl vinylcarbonate; and trimethylsilylmethyl vinyl carbonate.

An example of silicon-containing vinyl carbonate or vinyl carbamatemonomers are represented by Formula V:

wherein:

Y′ denotes —O—, —S— or —NH—;

R^(Si) denotes a silicon containing organic radical;

R₃ denotes hydrogen or methyl;

d is 1, 2, 3 or 4; and q is 0 or 1.

Suitable silicon containing organic radicals R^(Si) include thefollowing:

wherein:

R₄ denotes

wherein p′ is 1 to 6;

R₅ denotes an alkyl radical or a fluoroalkyl radical having 1 to 6carbon atoms;

e is 1 to 200; n′ is 1, 2, 3 or 4; and m′ is 0, 1, 2, 3, 4 or 5.

An example of a particular species within Formula V is represented byFormula VI.

Another class of silicon-containing monomers includespolyurethane-polysiloxane macromonomers (also sometimes referred to asprepolymers), which may have hard-soft-hard blocks like traditionalurethane elastomers. They may be end-capped with a hydrophilic monomersuch as HEMA. Examples of such silicon containing urethanes aredisclosed in a variety of publications, including Lai, Yu-Chin, “TheRole of Bulky Polysiloxanylalkyl Methacrylates inPolyurethane-Polysiloxane Hydrogels,” Journal of Applied PolymerScience, Vol. 60, 1193-1199 (1996). PCT Published Application No. WO96/31792 discloses examples of such monomers, which disclosure is herebyincorporated by reference in its entirety. Further examples of siliconcontaining urethane monomers are represented by Formulae VII and VIII:

E(*D*A*D*G)_(a)*D*A*D*E′; or   (VII)

E(*D*G*D*A)_(a)*D*G*D*E′;   (VIII)

wherein:

D denotes an alkyl diradical, an alkyl cycloalkyl diradical, acycloalkyl diradical, an aryl diradical or an alkylaryl diradical having6 to 30 carbon atoms;

G denotes an alkyl diradical, a cycloalkyl diradical, an alkylcycloalkyl diradical, an aryl diradical or an alkylaryl diradical having1 to 40 carbon atoms and which may contain ether, thio or amine linkagesin the main chain;

denotes a urethane or ureido linkage;

a is at least 1;

A denotes a divalent polymeric radical of Formula IX:

wherein:

-   -   each R_(s) independently denotes an alkyl or fluoro-substituted        alkyl group having 1 to 10 carbon atoms which may contain ether        linkages between carbon atoms;    -   m′ is at least 1; and    -   p is a number which provides a moiety weight of 400 to 10,000;    -   each of E and E′ independently denotes a polymerizable        unsaturated organic radical represented by Formula X:

wherein:

R₆ is hydrogen or methyl;

R₇ is hydrogen, an alkyl radical having 1 to 6 carbon atoms, or a—CO—Y—R₉ radical wherein Y is —O—, —S— or —NH—;

R₈ is a divalent alkylene radical having 1 to 10 carbon atoms;

R₉ is a alkyl radical having 1 to 12 carbon atoms;

X denotes —CO— or —OCO—;

Z denotes —O— or —NH—;

Ar denotes an aromatic radical having 6 to 30 carbon atoms;

w is 0 to 6; x is 0 or 1; y is 0 or 1; and z is 0 or 1.

A more specific example of a silicon containing urethane monomer isrepresented by Formula (XI):

wherein m is at least 1 and is preferably 3 or 4, a is at least 1 andpreferably is 1, p is a number which provides a moiety weight of 400 to10,000 and is preferably at least 30, R₁₀ is a diradical of adiisocyanate after removal of the isocyanate group, such as thediradical of isophorone diisocyanate, and each E″ is a group representedby:

A preferred silicon containing hydrogel material comprises (in the bulkmonomer mixture that is copolymerized) 5 to 50 percent, preferably 10 to25 percent, by weight of one or more silicon containing macromonomers, 5to 75 percent, preferably 30 to 60 percent, by weight of one or morepolysiloxanylalkyl(meth)acrylic monomers, and 10 to 50 percent,preferably 20 to 40 percent, by weight of a hydrophilic monomer. Ingeneral, the silicon containing macromonomer is a poly(organosiloxane)capped with an unsaturated group at two or more ends of the molecule. Inaddition to the end groups in the above structural formulas, U.S. Pat.No. 4,153,641 to Deichert et al. discloses additional unsaturatedgroups, including acryloxy or methacryloxy. Fumarate-containingmaterials such as those taught in U.S. Pat. Nos. 5,512,205; 5,449,729;and 5,310,779 to Lai are also useful substrates in accordance with theinvention. Preferably, the silane macromonomer is a silicon-containingvinyl carbonate or vinyl carbamate or a polyurethane-polysiloxane havingone or more hard-soft-hard blocks and end-capped with a hydrophilicmonomer.

Suitable hydrophilic monomers form hydrogels, such as silicon-containinghydrogel materials useful in the present invention. Examples of usefulmonomers include amides such as dimethylacrylamide,dimethylmethacrylamide, cyclic lactams such as n-vinyl-2-pyrrolidone andpoly(alkene glycols) functionalized with polymerizable groups. Examplesof useful functionalized poly(alkene glycols) include poly(diethyleneglycols) of varying chain length containing monomethacrylate ordimethacrylate end caps. In a preferred embodiment, the poly(alkeneglycol) polymer contains at least two alkene glycol monomeric units.Still further examples are the hydrophilic vinyl carbonate or vinylcarbamate monomers disclosed in U.S. Pat. No. 5,070,215, and thehydrophilic oxazolone monomers disclosed in U.S. Pat. No. 4,910,277.Other suitable hydrophilic monomers will be apparent to one skilled inthe art.

Device Forming Additives and Comonomers

The monomer mix may, further as necessary and within limits not toimpair the purpose and effect of the present invention, comprise variousadditives such as antioxidant, coloring agent, ultraviolet absorber andlubricant.

The monomer mix may be prepared by using, according to the end-use andthe like of the resulting shaped polymer articles, one or at least twoof the above comonomers and oligomers and, when occasions demand, one ormore crosslinking agents.

Where the shaped polymer articles are for example medical products, inparticular a contact lens, the monomer mix is suitably prepared from oneor more of the silicon compounds, e.g. siloxanyl(meth)acrylate,siloxanyl(meth)acrylamide and silicon containing oligomers, to obtaincontact lenses with high oxygen permeability.

The monomer mix may include additional constituents such as crosslinkingagents, internal wetting agents, hydrophilic monomeric units, tougheningagents, and other constituents as is well known in the art.

Although not required, the monomer mix may include toughening agents,preferably in quantities of less than about 80 weight percent e.g. fromabout 5 to about 80 weight percent, and more typically from about 20 toabout 60 weight percent. Examples of suitable toughening agents aredescribed in U.S. Pat. No. 4,327,203. These agents include cycloalkylacrylates or methacrylates, such as: methyl acrylate and methacrylate,t-butylcyclohexyl methacrylate, isopropylcyclopentyl acrylate,t-pentylcycloheptyl methacrylate, t-butylcyclohexyl acrylate,isohexylcyclopentyl acrylate and methylisopentyl cyclooctyl acrylate.Additional examples of suitable toughening agents are described in U.S.Pat. No. 4,355,147. This reference describes polycyclic acrylates ormethacrylates such as: isobornyl acrylate and methacrylate,dicyclopentadienyl acrylate and methacrylate, adamantyl acrylate andmethacrylate, and isopinocamphyl acrylate and methacrylate. Furtherexamples of toughening agents are provided in U.S. Pat. No. 5,270,418.This reference describes branched alkyl hydroxyl cycloalkyl acrylates,methacrylates, acrylamides and methacrylamides. Representative examplesinclude: 4-t-butyl-2-hydroxycyclohexyl methacrylate (TBE);4-t-butyl-2-hydroxycyclopentyl methacrylate;methacryloxyamino-4-t-butyl-2-hydroxycyclohexane;6-isopentyl-3-hydroxycyclohexyl methacrylate; andmethacryloxyamino-2-isohexyl-5-hydroxycyclopentane.

In particular regard to contact lenses, the fluorination of certainmonomers used in the formation of silicon containing hydrogels has beenindicated to reduce the accumulation of deposits on contact lenses madetherefrom, as described in U.S. Pat. Nos. 4,954,587, 5,079,319,5,010,141 and 6,891,010. Moreover, the use of silicon containingmonomers having certain fluorinated side groups, i.e. —(CF₂)—H, havebeen found to improve compatibility between the hydrophilic and siliconcontaining monomeric units, as described in U.S. Pat. Nos. 5,387,662 and5,321,108.

As stated above, surface structure and composition determine many of thephysical properties and ultimate uses of solid materials.Characteristics such as wetting, friction, and adhesion or lubricity arelargely influenced by surface characteristics. The alteration of surfacecharacteristics is of special significance in biotechnical applicationswhere biocompatibility is of particular concern. Thus, it is desired toprovide a silicon containing hydrogel contact lens with an opticallyclear, hydrophilic surface film that will not only exhibit improvedwettability, but which will generally allow the use of a siliconcontaining hydrogel contact lens in the human eye for extended period oftime. In the case of a silicon containing hydrogel lens for extendedwear, it be further desirable to provide an improved silicon-containinghydrogel contact lens with an optically clear surface film that will notonly exhibit improved lipid and microbial behavior, but which willgenerally allow the use of a silicon-containing hydrogel contact lens inthe human eye for an extended period of time. Such a surface treatedlens would be comfortable to wear in actual use and allow for theextended wear of the lens without irritation or other adverse effects tothe cornea.

It also may be desirable to apply these surface enhancing coatings toimplantable medical devices such as intraocular lens materials to reducethe attachment of lens epithelial cells to the implanted device and toreduce friction as the intraocular lens passes through an inserter intothe eye. It may also be desirable to apply these surface enhancingcoatings to surgical instruments such as intraocular lens inserters andendoscopic instruments.

Methods of coating the substrate would include dip coating of thesubstrate into a solution containing the surface modifying agent. Thesolution containing the surface modifying agent may containsubstantially the surface modifying agent in solvent or may containother materials such as cleaning and extracting materials. Other methodscould include spray coating the device with the surface modifying agent.Alternatively, the substrate and the other surface modifying agent maybe subjected to autoclave conditions. In certain embodiments, thesubstrate and the surface modifying agent may be autoclaved in thepackaging material that will contain the coated substrate. Once thecontact between the substrate and the surface modifying agent hasoccurred, the remaining surface modifying agent could be substantiallyremoved and packaging solution would be added to the substrate packagingmaterial. Sealing and other processing steps would then proceed as theyusually do. Alternatively, the surface modifying agent could be retainedin the substrate packaging material during storage and shipping of thesubstrate device to the end user.

A general method of coating is now described. Medical devices, such ascommercial SofLens₅₉™ contact lenses, are removed from the packaging andsoaked in purified water for at least 15 minutes prior to being placedin polymer solution. It should be recognized by persons skilled in theart that the quantities of a solution disclosed herein may be adjustedunder specific circumstances to accommodate the size of the medicaldevice. Glass vials are labeled and filled with about 4 ml of a polymersolution, and a lens is placed in each vial. When two polymer solutionsare used for coating, they are mixed together immediately prior toplacing in the vials. The vials are capped with silicone stoppers andcrimped aluminum caps, then placed in an autoclave for one 30-minutecycle. The treated lenses are allowed to cool for a minimum of 3 hours,then removed from the vials and rinsed at least three times withdeionized water. The rinsed lenses are then placed into new vialscontaining 4 ml of borate buffered saline (phosphate for samplesundergoing bacterial adhesion testing) and autoclaved for one 30-minutecycle for sterilization.

Other types of contact lenses, such as those comprising other hydrogelmaterials can be treated with coating polymers, as disclosed above. Inone embodiment, PureVision™ contact lenses comprising Balafilcon Ahydrogel material, disclosed in U.S. Pat. No. 5,260,000, which isincorporated herein by reference, are surface-treated with a coatingpolymer as disclosed above. (PureVision™ contact lenses are availablefrom Bausch and Lomb Incorporated, Rochester, N.Y.) In one aspect,PureVision™ contact lenses are first treated with a plasma dischargegenerated in a chamber containing air. A packaging solution for surfacetreatment comprised segmented block poly(TRIS-b-DMA) is added to ablister package before the lens is placed in and sealed around theperimeter of the receptacle with lidstock, The blister containing thelens is then autoclaved for one 30-minute cycle for sterilization.

In another method, a fluoro-silicone hydrogel contact lenses arepackaged in a container that includes a receptacle portion to hold thecontact lens and a sterile packaging solution comprising a segmentedblock poly(OFPMA-b-DMA). Examples of the container are conventionalcontact lens blister packages. This receptacle, containing the contactlens immersed in the solution, is hermetically sealed, for example, bysealing lidstock on the package over the receptacle. For example, thelidstock is sealed around a perimeter of the receptacle.

The solution and the contact lens are sterilized while sealed in thepackage receptacle. Examples of sterilization techniques includesubjecting the solution and the contact lens to thermal energy,microwave radiation, gamma radiation or ultraviolet radiation. Aspecific example involves heating the solution and the contact lens,while sealed in the package container, to a temperature of at least 100°C., more preferably at least 120° C., such as by autoclaving.

The packaging solution is an aqueous solution that includes the surfaceactive segmented block copolymer, preferably in an amount of 0.02 to 5.0weight percent, based on total weight of the packaging solution. Thespecific amount of surface active segmented block copolymer will varydepending on the substrate and the copolymer, but generally, the surfaceactive segmented block copolymer will be present in an amount withinthis range.

The packaging solutions preferably have a pH of about 6.0 to 8.0, morepreferably about 6.5 to 7.8, and most preferably 6.7 to 7.7. Suitablebuffers include monoethanolamine, diethanolamine, triethanolamine,tromethamine (tris(hydroxymethyl)aminomethane, Tris), Bis-Tris, Bis-TrisPropane, borate, citrate, phosphate, bicarbonate, amino acids, andmixtures thereof. Examples of specific buffering agents include boricacid, sodium borate, potassium citrate, citric acid, Bis-Tris, Bis-TrisPropane, and sodium bicarbonate. When present, buffers will generally beused in amounts ranging from about 0.05 to 2.5 percent by weight, andpreferably from 0.1 to 1.5 percent by weight.

The packaging solutions may further include a tonicity adjusting agent,optionally in the form of a buffering agent, for providing an isotonicor near-isotonic solution having an osmolality of about 200 to 400mOsm/kg, more preferably about 250 to 350 mOsm/kg. Examples of suitabletonicity adjusting agents include sodium and potassium chloride,dextrose, glycerin, calcium and magnesium chloride. When present, theseagents will generally be used in amounts ranging from about 0.01 to 2.5weight percent and preferably from about 0.2 to about 1.5 weightpercent.

Optionally, the packaging solutions may include an antimicrobial agent,but it is preferred that the solutions lack such an agent.

The surface active segmented block copolymers useful in certainembodiments of the present invention may be prepared according tosyntheses well known in the art and according to the methods disclosedin the following examples. Surface modification of contact lenses usingone or more surface modifying agents in accordance with the presentinvention is described in still greater detail in the examples thatfollow.

EXAMPLES Example A Synthesis of NVP-b-LMA Copolymer

To a 100-mL 2-neck round bottom flask equipped with a magnetic stir bar,2 septa and an SS sparging needle was added 44 mg of AIBN, 10.0-g (0.090mol) of N-vinylpyrrolidone (NVP), 0.20-g (0.00090 mol) ofethyl-α-(O-ethylxanthyl) propionate (EEXP) and 20-mL of 1,4-dioxane. Thesolution was sparged with nitrogen for 30-min. at RT before heating theflask in an oil bath to 60° C. The solution was sparged throughout theentire course of the polymerization. After 6 hours at 60° C., a 1 mLaliquot was removed from the flask and precipitated in 50 mL of ethylether. A quantity of lauryl methacrylate (LMA) (2.64-mL, 0.0090 mol) wasthen added to the flask in one portion via pipette. The solution wasmaintained at 60° C. overnight. The now hazy solution was cooled to RTand was added dropwise into 2.5-L of stirred ethyl ether. Theprecipitate was isolated by filtration and dried in vacuo at RTaffording 6.08-g (49%) of white solid. The 6-hour aliquot was isolatedin similar fashion.

The block copolymer product was characterized by proton NMR (CDC13) andGPC. Resonances attributable to the alkyl protons of LMA were observedat approximately 0.8 and 1.25 ppm (not present in spectrum of the PVPaliquot). GPC was performed using a PLgel RESIpore column and DMF+1.0 MLiBr as solvent with calibration using PVP standards. Mn for the PVPaliquot was determined to be 11,650 Daltons (target=11,340 Daltons) witha polydispersity of 1.44. Mn for the block copolymer was determined tobe 18,650 Daltons (target=13,900 Daltons) with a polydispersity of 1.63.

Example B Synthesis of NVP-b-TRIS-VC (Two Step)

AIBN (23.2 mgs; 1.41×10⁻⁴ mol) was added to a 100 mL Schlenk flaskequipped with a magnetic stirring bar. To the flask was added 147 mgs(7.05×10⁻⁴) of ethyl-α-(O-ethylxanthyl) propionate (EEXP) dissolved in asmall amount of dioxane. Dioxane (15 ml) and N-vinylpyrrolidone (NVP)[15 ml; 0.141 mol] were added to the Schlenk flask, which was thensealed and purged with N₂ for 30 minutes. The flask was placed in an oilbath (60° C.) for 24 hours. After cooling to RT, 20 ml of THF was addedto the flask and the reaction was precipitated into diethyl ether whilestirring vigorously. The precipitate was isolated by filtration anddried in vacuo yielding 14.148 grams of white solid (PVP MacroRAFTagent).

The second block (TRIS-VC) was added to the PVP MacroRAFT agent in asecond reaction. Ten grams of PVP MacroRAFT agent (approx. 1.67×10⁻³mol) was added to a 100 mL Schlenk flask along with 20 mL of 1,4-dioxaneand a stir bar. 14.127-g (3.3×10⁻² mol) of TRIS-VC and 54.8 mgs of AIBN(3.33×10⁻⁴ mol) were then added to the flask which was sealed and purgedwith N₂ for 60 minutes. The reaction was then heated for 11 hours in a60° C. oil bath. The reaction mixture was dissolved in methanol(creating a dispersion). Dialysis tubes (Spectra/por 6, MWCO 3500) werefilled with the solution and submerged in 1 L of methanol solvent withslow stirring. The solvent was changed after 4 h, 19.5 h, and 41.5 h.The tubes were removed at 48 h and the methanol was removed with arotary evaporator. The resulting polymer was dried in a vacuum oven.

Both the PVP MacroRAFT agent and the block copolymer of NVP and TRIS-VCwere characterized by proton NMR (CDC13) and GPC. The calculatedmolecular weight of the block copolymer (MW=10,640 PD=1.30) is higherthan the PVP MacroRAFT agent (MW=6,760). In addition, the NMR spectrumof the block copolymer shows peaks present from the TRIS-VC block at 0.0ppm and 0.3 ppm and distinct peaks from the PVP segments between 1.0-2.5ppm and 3.0-4.0 ppm. From the integrations it is estimated that theratio of NVP:TRIS-VC is approximated at 29:1 by NMR.

Example C Synthesis of NVP-b-TRIS-VC (Sequential Addition)

NVP (10 ml; 0.09 mol.), Xanthate (0.094 g, 4.5×10⁻⁴ mol.), AIBN (15 mg,9.0×10-5 mol.), and 1,4 dioxane (10 ml) were added to Schlenk flask. Theflask was sealed and purged with N2 for 1 hour. The flask was thenheated at 60° C. for 22 hours. In a separate flask, TRIS-VC (3.81 g,8.99×10-3 mol.), AIBN (15 mg, 9.0×10-5 mol.) and 1,4-dioxane (4 ml) werecombined, and then the flask was sealed and purged with N2 for 1 hour.This solution was then carefully added to the PVP reaction under N2. Theflask was then heated for another 21 hours. Conversion of TRIS-VC wasmeasured to be 35% by NMR. After cooling, methanol was added and thesolution dialyzed (Spectra/por 6, MWCO 3500). The tubes were removed at40 h and the methanol removed. The polymer was dried in a vacuum oven.The 1 H NMR spectrum indicates a composition of approximately 4% ofTRIS-VC, a similar value to the block copolymer in example B (ratio ofNVP:TRIS-VC is approximated at 29:1).

Note* This approach should yield a block copolymer that has the changefrom one segment to the other less well-defined as the first blockcopolymer discussed above The second block may actually be a statisticalcopolymerization of the TRIS-VC and any remaining NVP that had not beenpolymerized at the time of the TRIS-VC addition. The second “block”, istherefore compositionally heterogeneous. A polymerization that yields astatistical copolymerization or compositionally heterogeneous block asthe second block would also be considered to be a reactive segmentedblock copolymer according to the invention herein.

Example D Synthesis of various DMA-b-Hydrophobic monomer (SequentialAddition)

Hydrophobic DMA DMA CTR CTR Methacrylate Reaction (mL) (mol) (mgs) (mol)(ml) HM (mol) 2748-152 10 0.097 175 0.00048 1.40 0.0049 2748-153 100.097 175 0.00048 2.12 0.0073 2748-154 10 0.097 350 0.00097 2.12 0.00732748-155 10 0.097 350 0.00097 2.80 0.0097 2748-156 10 0.097 88 0.000241.12 0.0039 2748-157 10 0.097 88 0.00024 1.70 0.0058 *For reactions-152,-154, and -156 the hydrophobic methacrylate was3,3,4,4,5,5,6,6,7,7,8,8-tridecafluorooctyl methacrylate (TDFM). *Forreactions-153, -155, and -157 the hydrophobic methacrylate was laurylmethacrylate (LMA).

Note: All reactions were carried out in a similar fashion using theamounts shown in the table above. Reaction 2748-152 is described belowas an example of the procedure used. Weighed 175 mgs (0.48 mmol) ofS-1-Dodecyl-S-(α,α′-dimethyl-α″-acetic acid) trithiocarbonate and 35 mgsof AIBN into a 250 ml round bottom flask. Added 10 ml (97 mmol) ofN,N-Dimethylacrylamide (DMA) and 30 ml of dioxane to the flask, sealedflask with a septum and then purged with argon to deoxygenate for 30mins. Placed flask in an oil bath (50° C.) for 6.0 hrs. In a separatecontainer, 1.40 ml (4.9 mmol) of3,3,4,4,5,5,6,6,7,7,8,8-tridecafluorooctyl methacrylate (TDFM) wasbubbled with argon for 30 mins., then added to the flask after 6.0 hrs.*Note: A small aliquot was taken from the flask immediately before TDFMaddition and precipitated into diethyl ether. The reaction was stopped16 hours after TDFM addition (22 hrs total reaction time). The finalproduct was precipitated out of the reaction mixture into diethyl ether.Precipitate contained a cloudy layer in the diethyl ether that wasdecanted off and a precipitate that settled that was collected and driedin the vacuum oven.

For all of the reactions, both the first precipitate and the blockcopolymer of DMA and hydrophobic methacrylate (either TDFM or LMA) werecharacterized by proton NMR (CDC13) and GPC (DMF as eluent). The GPCchromatograms all show a shift in the elution peaks to shorter times(higher MW) after the addition of the hydrophobic methacrylate blocks.In addition, the NMR spectra of the block copolymers for samples −152,−154, and −156 above show a broad peak at around 4.5 ppm correspondingto the methylene group adjacent to the methacrylate of3,3,4,4,5,5,6,6,7,7,8,8-tridecafluorooctyl methacrylate (TDFM). The NMRof the block copolymers for samples −153, −155, and −157 show peaks forthe —CH3 group (0.8 ppm) and —CH2- groups (1.3 ppm) of the alkyl chainof lauryl methacrylate

Example E Synthesis of a Matrix of GMA-b-DMA Copolymers where the MW ofEach of the Blocks is Varied

TABLE 5 MW DMA MW GMA DMA DMA CTR CTR GMA GMA block block Reaction (mL)(mol) (mgs) (mol) (mL) (mol) (theoretical) (theoretical) 2748-114 200.194 350 0.00097 2.0 0.0146 19,800 2,140 2748-115 20 0.194 350 0.000974.0 0.0293 19,800 4,275 2748-116 20 0.194 350 0.00097 8.0 0.0586 19,8008,550 2748-117 20 0.194 700 0.00194 2.0 0.0146 9,900 1,070 2748-118 200.194 700 0.00194 4.0 0.0293 9,900 2,140 2748-119 20 0.194 700 0.001948.0 0.0586 9,900 4,275 2748-120 10 0.097 700 0.00194 2.0 0.0146 4,9501,070 2748-121 10 0.097 700 0.00194 4.0 0.0293 4,950 2,140 2748-122 100.097 700 0.00194 8.0 0.0586 4,950 4,275 *~33 mgs of AIBN were added toall of the reactions

*Note: All reactions were carried out in a similiar fashion using theamounts shown in the table above. Reaction 2748-1114 is described belowas an example of the procedure used. Weighed 350 mgs (0.97 mmol) ofS-1Dodecyl-S-(q α′-dimethyl-α″-acetic acid) trithiocarbonate and 33 mgsof AIBN into a 250 ml round bottom flask. Added 20 ml (194 mmol) ofN,N-Dimethylacrylamide (DMA) and 60 ml of dioxane to the flask, sealedflask with a septum and then purged with argon to deoxygenate for 30mins. Placed flask in an oil bath (50° C.) for 6.0 hrs. In a separatecontainer, 2.0 ml (14.66 mmol) of glycidyl methacrylate (GMA) wasbubbled with argon for 30 mins., then added to the flask after 6.0 hrs.*Note: A small aliquot was taken from the flask immediately before GMAaddition and precipitated into diethyl ether. The reaction was stopped15 hours after GMA addition (19.5 hrs total reaction time). The finalproduct was precipitated out of the reaction mixture into diethyl ether.

Both the first precipitate and the block copolymer of DMA and GMA werecharacterized by proton NMR (CDC13) and GPC. The GPC shows a shift inthe elution peak to shorter times (higher MW) after the addition of theGMA block. In addition, the NMR spectra of the block copolymer showpeaks for the glycidol methacrylate contributions at 3.7 ppm and 4.3ppm. GPC data for these polymers using DMF as an eluent are shown below,using both PMMA standards and PVP standards as calibrants. Although thetrends in MW are the same, PMMA standards show MW's much closer to thetheoretically expected value for polyDMA.

TABLE 6 PMMA Standards PVP Standards Sample Mw Mn Mw Mn 2748-114 20,270 15,320  432,500 207,100 2748-115 — — 534,200 219,500 2748-116 — —681,500 282,000 2748-117 8,950 6,430 147,800 71,700 2748-118 — — 182,40074,100 2748-119 — — 245,900 72,300 2748-120 4,000 2,540 48,600 16,1002748-121 — — 70,100 15,000 2748-122 — — 145,100 20,0

Example F Packaging a Lens with a Surfactant

An aqueous packaging solution containing 1% by weight of thesilicone-containing surfactant NVP-b-TRIS-VC of Example 1 dissolved in aborate buffered saline at a pH of 7.2 is placed in a polypropyleneblister package. Next, a balafilcon A contact lens is immersed in theaqueous packaging solution in the polypropylene blister package. Thepackage is sealed with foil lidstock and then autoclaved for 30 minutesat 121° C.

While there is shown and described herein certain specific structuresand compositions of the present invention, it will be manifest to thoseskilled in the art that various modifications may be made withoutdeparting from the spirit and scope of the underlying inventive conceptand that the same is not limited to particular structures herein shownand described except insofar as indicated by the scope of the appendedclaims.

1. A method of forming a surface modified medical device, the methodcomprising: providing a medical device having at least one surface;providing a surface modifying agent comprising a surface activesegmented block copolymer; and contacting the at least one surface ofthe medical device with the surface modifying agent to form a surfacemodified medical device.
 2. The method of claim 1 wherein the medicaldevice comprises a silicon containing monomer.
 3. The method of claim 2wherein the silicon containing monomer comprises a silicon containingmonomer selected from the group consisting of silicon containing vinylcarbonates, silicon containing vinyl carbamates,polyurethane-polysiloxanes having one or more hard-soft-hard blocks andend-capped with a hydrophilic monomer, fumarate containing siliconcontaining monomers, poly(organosiloxanes) capped with an unsaturatedgroup at two or more ends of the molecule, polyurethane-polysiloxanemacromonomers and mixtures thereof.
 4. The method of claim 1 wherein themedical device comprises hydrogel materials.
 5. The method of claim 2wherein the medical device comprises silicon containing hydrogelmaterials.
 6. The method of claim 1 wherein the medical device comprisesvinyl functionalized polydimethylsiloxanes copolymerized withhydrophilic monomers.
 7. The method of claim 1 wherein the medicaldevice comprises a fluorinated monomer.
 8. The method of claim 7 whereinthe fluorinated monomer is selected from the group consisting ofmethacrylate functionalized fluorinated polyethylene oxides,fluoroalkylmethacrylates, and mixtures thereof.
 9. The method of claim 1wherein the medical device is selected from the group consisting ofheart valves, intraocular lenses, intraocular lens inserter, contactlenses, intrauterine devices, vessel substitutes, artificial ureters,vascular stents, phakic intraocular lenses, aphakic intraocular lenses,corneal implants, catheters, implants, endoscopic instruments, andartificial breast tissue.
 10. The method of claim 9 wherein the medicaldevice formed is a soft contact lens.
 11. The method of claim 10 whereinthe medical device is a silicon containing hydrogel contact lensmaterial.
 12. The method of claim 1 wherein the reactive segmented blockcopolymer has the following generic formula (I):R1-[(A)m]p-[(B)n]q-X   (I) wherein R1 is a reactive residue of a moietycapable of acting as an initiator for Atom Transfer RadicalPolymerization, A is a hydrophobic unit block, B is a hydrophilic unitblock, m is 1 to 10,000, n is 1 to 10,000, p and q are natural numbers,and X is a halogen capping group of an initiator for Atom TransferRadical Polymerization or a derivatized reaction product.
 13. The methodof claim 1 wherein the reactive segmented block copolymer has thefollowing generic formula (II):R1-[(A)m]p-[(B)n]q-R2   (II) wherein R1 is a radical forming residue ofa RAFT agent or free radical initiator, A is a hydrophobic unit block, Bis a hydrophilic unit block, m is 1 to 10,000, n is 1 to 10,000, p and qare natural numbers, and R2 is a thio carbonyl thio fragment of thechain transfer agent or a derivatized reaction product.
 14. The methodof claim 1 wherein the interactive segmented block copolymer has thefollowing generic formula (III):R1-[(B)n]q-[(A)m]p-R2-[(A)m]p-[(B)n]q-R1   (III) wherein R1 is a radicalforming residue of a RAFT agent or free radical initiator, A is ahydrophobic unit block, B is a hydrophilic unit block, m is 1 to 10,000,n is 1 to 10,000, p and q are natural numbers, and R2 is a thio carbonylthio group.
 15. The method of claim 1, wherein the hydrophobic unit ofthe surface active segmented block copolymer comprises a monomerselected from the group consisting of alkyl acrylates, hexylmethacrylate, lauryl methacrylate, fluoroacrylates,octofluoropentamethacrylate, 3,3,4,4,5,5,6,6,7,7,8,8-tridecafluorooctylmethacrylate, polysiloxanylalkyl(meth)acrylic monomers, M1-MCR-C12,methacryloxypropyl tris(trimethyl-siloxy)silane,tris(trimethylsiloxy)silylpropyl methacrylate, 3-(trimethylsilyl)propylvinyl carbonate;3-(vinyloxycarbonylthio)propyl-[tris(trimethylsiloxy)silane];3-[tris(tri-methylsiloxy)silyl]propyl vinyl carbamate;3-[tris(trimethylsiloxy)silyl]propyl allyl carbamate;3-[tris(trimethylsiloxy)silyl]propyl vinyl carbonate, dodecylmethacrylate, hexyl vinyl carbamate, hexyl vinyl carbonate,octafluoropentamethacrylate, octafluoropenta vinyl carbamate, andmixtures thereof.
 16. The method of claim 1, wherein the reactivesegmented block copolymer comprises a hydrophilic unit monomer selectedfrom the group consisting of 2-hydroxyethyl methacrylate, glycerolmethacrylate, methacrylic acid, acrylic acid, methacrylamide,acrylamide, N,N′-dimethylmethacrylamide, N,N′-dimethylacrylamide;ethylenically unsaturated poly(alkylene oxide)s, cyclic lactams,N-vinyl-2-pyrrolidone, hydrophilic vinyl carbonate, hydrophilic vinylcarbamate monomers, 2-hydroxyethyl acrylate,2-(2-ethoxyethoxy)ethyl(meth)acrylate, glyceryl(meth)acrylate,poly(ethylene glycol(meth)acrylate), tetrahydrofurfuryl(meth)acrylate,N-vinyl acetamide, copolymers, derivatives and combinations thereof. 17.The method of claim 1, wherein the surface active segmented blockcopolymer has a hydrophobic unit comprises between 1 and about 1,000units.
 18. The method of claim 1, wherein the surface active segmentedblock copolymer has a hydrophobic unit comprises between 1 and about 100units.
 19. The method of claim 1, wherein the surface active segmentedblock copolymer has a hydrophobic unit comprising between 1 and about 30units.
 20. The method of claim 1, wherein the surface active segmentedblock copolymer has a hydrophilic block comprising between 1 and about10,000 units.
 21. The method of claim 1, wherein the surface activesegmented block copolymer has a hydrophilic block comprising betweenabout 10 and about 1,000 units.
 22. The method of claim 1, wherein thesurface active segmented block copolymer has a hydrophilic blockcomprising between about 20 and about 300 units.
 23. A surface modifiedmedical device comprising: a medical device; and a surface activesegmented block copolymer comprising a hydrophobic unit block comprisingvinylically unsaturated polymerizable monomers and a hydrophilic blockcomprising vinylically unsaturated polymerizable monomers applied to thesurface of the medical device.
 24. The surface modified medical deviceof claim 23 wherein the medical device is a contact lens.
 25. Thesurface modified medical device of claim 24 wherein the medical deviceis a hydrophilic contact lens.
 26. The surface modified medical deviceof claim 24 wherein the medical device is a hydrogel contact lens. 27.The method of claim 12 wherein the hydrophobic unit block comprisesvinylically unsaturated polymerizable monomers and the hydrophilic blockcomprises vinylically unsaturated polymerizable monomers.
 28. The methodof claim 13 wherein the hydrophobic unit block comprises vinylicallyunsaturated polymerizable monomers and the hydrophilic block comprisesvinylically unsaturated polymerizable monomers.
 29. The method of claim14 wherein the hydrophobic unit block comprises vinylically unsaturatedpolymerizable monomers and the hydrophilic block comprises vinylicallyunsaturated polymerizable monomers.